Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene) -1H-pyrrol-2(5H)-ones

Article abstract of DOI:10.1016/j.tetlet.2010.07.073

The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H- pyrrol-2(5H)-ones 5, 6a-d from 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2- oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a-d is reported. The 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropyl

Full text of DOI:10.1016/j.tetlet.2010.07.073

Tetrahedron Letters 51 (2010) 4908–4910
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Efficient synthesis of new 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-
1H-pyrrol-2(5H)-ones
b
c
a
a
Alex F. C. Flores a, , Lucas Pizzuti , Luciana A. Piovesan , Darlene C. Flores , Juliana L. Malavolta ,
*
Claudio M. P. Pereira d
a Universidade Federal de Santa Maria, Departamento de Química, NUQUIMHE, 97105-900 Santa Maria, RS, Brazil
b Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, Km 12, Unidade II, Caixa Postal 533, 79804-970 Dourados, MS, Brazil
c Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Laboratório de Avaliação e Síntese de Substâncias Bioativas, LASSBio, Cidade Universitária,
21941-590 Rio de Janeiro, RJ, Brazil
d Universidade Federal de Pelotas, Instituto de Química e Geociências, Campus Universitário, Caixa-Postal 354, 96010-900 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-ones 5, 6a–d from
1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a–d is reported. The
1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones 3, 4a–d were obtained
from regiospecific bromination of 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones
1, 2a–d with molecular bromine. The NMR and X-ray diffraction data showed that 1-alkyl(aryl)-5-(3,3,3-
trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones were brominated at 4-position in the pyrrolidin-2-one
ring.
Received 20 May 2010
Revised 12 July 2010
Accepted 13 July 2010
Available online 18 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Our continuing interest in 1,3-dielectrophilic compounds has led
us to study a new aspect of the application of the acetal acylation
method for producing methyl 4-methoxy-6-oxo-7,7,7-trihalo-4-
heptenoates 1 and 2.1 These 1,3-dielectrophilic precursors have
proved to be important building blocks for regiospecific synthesis
of heterocyclic compounds bearing trihalomethyl group with
important pharmacological and synthetic applications.2 Recently,
the synthesis of 5-bromo-1,1,1-trichloro-(fluoro)-4-methoxy pent-
3-en-2-ones, obtained from bromination of the parent enones, has
been developed, in analytical purity and good yields.3
ene)-1H-pyrrol-2(5H)-ones (5a–d, 6a–d). The starting 1-alkyl
(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones
(1a–d, 2a–d) were prepared from the corresponding methyl 4-
methoxy-6-oxo-7,7,7-trihalo-4-heptenoates reacting with primary
alkyl and aryl amines.1
The precursors 1a–d and 2a–d have two obvious nucleophilic
sites, 1-position at propylidene chain and 3-position at pyrroli-
din-2-one ring. However, we observed that the electrophilic bro-
mine, from molecular bromine, reacted exclusively at 4-position
in pyrrolidin-2-one ring, the reactive nucleophilic site under used
conditions (Scheme 1). The monobromination was instantaneous
without acid catalysis, as soon as the bromine was added to pyrr-
On the other hand, the importance of the pyrrole ring has con-
tinued to stimulate a great deal of interest in the development of
new methodologies for its synthesis.4–8 Pyrrolin-2-ones are biolog-
ically active compounds, which are important structural units in
alkaloids, nucleosides, antineoplastic agents or immunosuppres-
Br
O
O
i, ii
sants.9–12 In 3-pyrrolin-2-ones, the
a,b-unsaturated lactam moiety
X3C
X3C
O
O
N
R
N
R
can be utilized as a Michael acceptor for a variety of nucleophiles,
including carbon and nitrogen nucleophiles. In addition pyrrolidin-
2-ones can be utilized as precursors for a variety of heterocycles,
including 3-(3-azolyl)propanoates and 3-(3-azolyl)propanamides.2,13
Herein, we wish to report an efficient approach for the synthesis
of 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-
pyrrolidin-2-ones (3a–d, 4a–d) from the corresponding 1-alkyl
(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrolidin-2-ones
(1a–d, 2a–d), and their subsequent dehydrobromination with
triethylamine to the 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylid-
1a-d, 2a-d
3a-d, 4a-d
iii
1, 3, 5
F
2, 4, 6
Cl
O
X
X3C
d
b
c
a
O
N
R
R
Pr CH2Ph
Ph 4-BrC6H4
5a-d, 6a-d
* Corresponding author. Tel.: +55 3220 8741; fax: +55 3220 8031.
E-mail address: alexflores@smail.ufsm.br (A.F.C. Flores).
Scheme 1. Reagents and conditions: (i) Br2, CH2Cl2, 25 °C, 4 h; (ii) pyridine, 0–25 °C,
30 min; (iii) Et3N, CH2Cl2, 25 °C, 15 min.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.073

A. F. C. Flores et al. / Tetrahedron Letters 51 (2010) 4908–4910
4909
olidin-2-ne solution, the red coloration was lost and the HBr was
Br Br
H
released. The 1H NMR data have demonstrated that the brominated
products 3 and 4 are pure. The unambiguous 1H and 13C NMR
chemical shift assignments of compounds 3a–d and 4a–d were ob-
tained with the help of 2D and DEPT 135 NMR experiments. The
structure of 3d was elucidated by an X-ray crystallographic analy-
sis (Fig. 1).14 Given the novelty of the NMR assignment for bromi-
nated 5-(3,3,3-trifluoro-2-oxopropylidene)-1H-pyrrolidin-2-ones
we are pleased that these assignments could be validated by
X-ray crystallographic result.
O
O
X3C
X3C
O
O
N
N
R
R
1, 2
-PyHBr
Py
Br
1, 3 2, 4
O
X
F
Cl
X3C
Compounds 3a–d and 4a–d show 1H chemical shifts of the dia-
stereotopic methylene hydrogens (H-3) as a characteristic ABX sys-
tem, a doublet at 3.1 ppm with a geminal coupling constant at
2J = 19 Hz from hydrogen cis to the bromine atom and a double
doublet at 3.32 ppm with a vicinal coupling constant at 3J = 7 Hz
and a geminal coupling constant at 2J = 19 Hz from hydrogen trans
to bromine. The signal from the H-4 was a doublet at the range of
5.75–5.90 ppm with 3J = 7 Hz. The signal characteristic of vinylic
hydrogen at the propylidene moiety was observed as a singlet at
5.6–5.8 ppm. The 13C NMR spectra showed the signals of the pro-
pylidene moiety at characteristic regions, CF3 at 117 ppm as a
quartet with JCF = 292 Hz or CCl3 as a low intense signal at
96 ppm, C-sp2 at 91–94 ppm and carbonyl at the range of 177–
178 ppm as a quartet with JCF = 35 Hz for 3a–d, and carbonyl at
178–180 ppm for 4a–d. Brominated carbon was observed at a
range of 36 ppm in lower field than signal for C-3 at range 40 ppm.
A proposed mechanism for bromination of 1a–d and 2a–d could
involve a tautomerization as showed in Scheme 2.
O
N
R
3, 4
Scheme 2.
116 ppm as a quartet with JCF = 291 Hz or CCl3 as a low intense sig-
nal at 96.5 ppm, C-6 at 96–98 ppm and carbonyl C-7 at the range of
179–180 ppm as a quartet with JCF = 35 Hz for 5a–d, and as a short
singlet at 178–180 ppm 6a–d. Carbons C-3 and C-4 from the pyrro-
lone ring were observed, respectively, at the range of 136 and
128 ppm, typical chemical shifts for vinylic C-sp2.
The HBr elimination from 3 and 4 with triethylamine furnished
1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxopropylidene)-1H-pyrrol-2(5H)-
ones 5 and 6 in a short reaction time (15 min) in quantitative yield.
The structure of the synthesized products has been confirmed by
mass spectrometry and 1H and 13C NMR spectroscopy. The mecha-
nism involves two possibilities including classical E2 elimination,
with Et3N attack to trans bromine hydrogen and concerted output
of the bromide, or E1cB elimination with amide enolate formation
followed for bromide elimination. It still remains unknown, but
investigations are currently in progress (Scheme 3).
In conclusion, we report a convenient synthesis of a new series
of 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylidene)-1H-
pyrrolidin-2-ones and 1-alkyl(aryl)-5-(3,3,3-tri halo-2-oxopr-
opylidene)-1H-pyrrol-2(5H)-ones. 1-Alkyl (aryl)-4-bromo-5-(3,3,
3-trihalo-2-oxopropylidene)-1H-pyr rolidin-2-ones were regiospecif-
ically brominated with molecular bromine under mild conditions
furnishing good yields of products which were dehydrobrominated
under alkaline conditions using Et3N. This approach shows a clear
advantage over the methods reported in the literature where the
The compounds 5a–d and 6a–d show 1H chemical shifts of the
vinylic hydrogens, H-3 as a doublet at 8.2 ppm with a cis coupling
constant at 3J = 6 Hz, and H-4 as a doublet of doublets at 6.5 ppm
with a cis coupling constant at 3J = 6 Hz and a coupling constant
4J = 1 Hz from hydrogen at the propylidene moiety H-6. The signal
from vinylic hydrogen H-6 was observed as a tin doublet with
4J = 1 Hz, for trifluorinated derivatives at 5.9 ppm and for trichlori-
nated derivatives at 6.3 ppm. The 13C NMR spectra showed the
signals of the propylidene moiety at characteristic regions, CF3 at
Et3N
O
trans
H
Br
+
O
- Et3NHBr
X3C
O
X3C
N
R
O
N
R
E2
5, 6
3, 4
-Br
4,6
Cl
3,5
Br
X
F
O
X3C
-
O
N
R
Et3N
H
Br
Br
+
O
O
-
- Et3NH
X3C
X3C
O
O
E1cB
N
R
N
R
3, 4
Figure 1. X-ray molecular structure of compound 6a in representation of atoms via
thermal ellipsoids at 50% probability level.
Scheme 3.

4910
A. F. C. Flores et al. / Tetrahedron Letters 51 (2010) 4908–4910
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Fax +44 0 1223
336033, email: deposit@ccdc.cam.ac.uk.
15. Snider, B. B.; Neubert, B. J. J. Org. Chem. 2004, 69, 8953–8955.
synthesis of functionalized 5-propylidene-1H-pyrrolidin-2-one
derivatives was obtained in several reaction steps, or using expen-
sive reagents.6–12,15
All common reagents and solvents were used as obtained from
commercial suppliers without further purification. All melting points
were determined on a Reichert Thermovar apparatus and are uncor-
rected. 1H and 13C NMR spectra were acquired on a Bruker DPX
400spectrometer (1H at 400.13 MHz and 13C at 100.63 MHz), 5 mm
sample tubes, 298 K, digital resolution 0.01 ppm, in CDCl3, and
TMS as internal reference.
The general procedure for 1-alkyl(aryl)-4-bromo-5-(3,3,3-tri-
halo-2-oxopropylidene)-1H-pyrrolidin-2-ones (3a–d, 4a–d) with
molecular bromine: to a stirred solution of 1-alkyl(aryl)-5-(3,3,3-tri-
halo-2-oxopropylidene)-1H-pyrroli din-2-one (2 mmol) in methy-
lene chloride (5 mL) was added dropwise a solution of molecular
bromine in methylene chloride. The mixture was stirred for 4 h at
room temperature. Then the mixture was cooled in ice bath, at
À4 °C, and to which was added a solution with pyridine (2 mmol)
in methylene chloride. The resulting solution was stirred for
30 min. Then, it was washed with water (3 Â 15 mL), and the organ-
ic layer was dried over Na2SO4. The solvent was evaporated to give
pure products 3a–d and 4a–d. Products were fully characterized by
elemental analysis and NMR data.16
16. For 3a: 86%, red-brown oil, 1H NMR d 5.85 (s, 1H, H-6), 5.78 (d, 1H, JHH = 7 Hz,
H-4), 3.75 (m, 1H, H-9), 3.52 (m, 1H, H-9), 3.26 (dd, 1H, JHH = 19 and 7 Hz, H-3),
3.03 (d, 1H, JHH = 19 Hz, H-3), 1.69 (sx, 2H, JHH = 7 Hz, H-10), 0.99 (t, 3H,
JHH = 7 Hz, H-11). 13C NMR d 177.7 (q, JCF = 35 Hz, C-7), 173 (C-5), 165.6 (C-2),
116.1 (q, JCF = 291 Hz, C-8), 91.5 (C-6), 42.4 (C-9), 39.7 (C-3), 36 (C-4), 19.4 (C-10),
11 (C-11). MS m/z (%) 315(M++2, 10), 313 (M+, 8), 244 (39), 234 (100), 204 (15),
108 (35). Compound 3b: 91%, red oil, 1H NMR d 7.38–7.23 (m, 5H, Ph), 5.81 (s, 1H,
H-6), 5.75 (d, 1H, JHH = 7 Hz, H-4), 4.95 (d, 1H, JHH = 16 Hz, H-9), 4.71 (d, 1H,
JHH = 16 Hz, H-9), 3.32 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.09 (d, 1H, JHH = 19 Hz,
H-3). 13C NMR d 177.6 (q, JCF = 35 Hz, C-7), 172.9 (C-5), 164.7 (C-2), 133, 129, 128.3,
127 (Ph), 115.9 (q, JCF = 291 Hz, C-8), 92.8 (C-6), 44.4 (C-9), 39.7 (C-3), 35.9 (C-4).
MS m/z (%) 364(M++2, <5), 362 (M+, <5), 292 (9), 282 (100), 204 (15), 91 (67).
Compound 3c: 90%, white solid, mp 77–79 °C, 1H NMR d 7.61–7.24 (m, 5H, Ph),
5.89 (d, 1H, JHH = 7 Hz, H-4), 5.66 (d, 1H, H-6), 3.44 (dd, 1H, JHH = 19 and 7 Hz, H-
3), 3.16 (d, 1H, JHH = 19 Hz, H-3). 13C NMR d 178.2 (q, JCF = 35 Hz, C-7), 172.3 (C-5),
166.4 (C-2), 132.4, 130.2, 130, 126.9 (Ph), 115.9 (q, JCF = 291 Hz, C-8), 93.3 (C-6),
40.1 (C-3), 36.2 (C-3). MS m/z (%) 349(M++2, <5), 347 (M+, <5), 278 (9), 268 (16),
198 (75), 170 (38), 144 (22), 77 (100). Compound 3d: 80%, yellow solid, mp 139–
141 °C, 1H NMR d 7.72 (m, 2H, Ar), 7.15 (m, 2H, Ar), 5.89 (d, 1H, JHH = 7 Hz, H-4),
5.67 (d, 1H, H-6), 3.43 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.17 (d, 1H, JHH = 19 Hz, H-
3). 13C NMR d 178 (q, JCF = 35 Hz, C-7), 172 (C-5), 165.9 (C-2), 133.5, 131.3, 128.5,
120.1 (Ar), 115.8 (q, JCF = 291 Hz, C-8), 93.2 (C-6), 40 (C-4), 36.1 (C-3). Compound
4a: 79%, brown oil, 1H NMR d 6.15 (s, 1H, H-6), 5.83 (d, 1H, JHH = 7 Hz, H-4), 3.78
(m, 1H, H-9), 3.53 (m, 1H, H-9), 3.26 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.03 (d, 1H,
JHH = 19 Hz, H-3), 1.70 (sx, 2H, JHH = 7 Hz, H-10), 0.99 (t, 3H, JHH = 7 Hz, H-11). 13
C
NMR d 178.7 (C-7), 172.8 (C-5), 164.3 (C-2), 96.9 (C-8), 91.4 (C-6), 42.3 (C-9), 39.9
(C-3), 35.9 (C-4), 19.5 (C-10), 11.1 (C-11). MS m/z (%) 364(M++2, <5), 362 (M+, <5),
246 (100), 244 (90), 204 (13), 202 (10), 164 (55), 122 (58), 80 (20), 78 (18).
Compound 4b: 97%, brown oil, 1H NMR d 7.37–7.25 (m, 5H, Ph), 6.11 (s, 1H, H-6),
5.79 (d, 1H, JHH = 7 Hz, H-4), 4.98 (d, 1H, JHH = 16 Hz, H-9), 4.74 (d, 1H,
JHH = 16 Hz, H-9), 3.33 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.11 (d, 1H, JHH = 19 Hz,
H-3). 13C NMR d 178.5 (C-7), 172.8 (C-5), 163.1 (C-2), 133.3, 129, 128.3, 127.3
(Ph), 96.7 (C-8), 93.1 (C-6), 44.5 (C-9), 40 (C-3), 35.7 (C-4). Compound 4c: 89%,
yellow solid, mp 118–120 °C, 1H NMR d 7.60–7.27 (m, 5H, Ph), 5.99 (d, 1H, H-6),
5.95 (d, 1H, JHH = 7 Hz, H-4), 3.47 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.17 (d, 1H,
JHH = 19 Hz, H-3). 13C NMR d 179 (C-7), 172.1 (C-5), 165.2 (C-2), 132.7, 130.1,
129.8, 126.9 (Ph), 96.6 (q, JCF = 291 Hz, C-8), 93.3 (C-6), 40.4 (C-3), 36.2 (C-4).
Compound 4d: 91%, yellow solid, mp 146–148 °C, 1H NMR d 7.75 (m, 2H, Ar), 7.14
(m, 2H, Ar), 5.99 (d, 1H, H-6), 5.94 (d, 1H, JHH = 7 Hz, H-4), 3.46 (dd, 1H, JHH = 19
and 7 Hz, H-3), 3.17 (d, 1H, JHH = 19 Hz, H-3). 13C NMR d 178.9 (q, JCF = 35 Hz, C-7),
171.8 (C-5), 164.5 (C-2), 133.4, 131.7, 128.5, 123.9 (Ar), 96.5 (C-8), 93.4 (C-6),
40.3 (C-4), 36 (C-3).
The general procedure for 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxo-
propylidene)-1H-pyrrol-2(5H)-ones (5a–d, 6a–d): to
a stirred
solution of 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylid-
ene)-1H-pyrrolidin-2-one (2 mmol) in methylene chloride (5 mL)
at 0 °C was dropwise added a solution of triethylamine (2.1 mmol)
in methylene chloride (5 mL). The mixture was stirred for 15 min.
Then the mixture was washed with water (3 Â 15 mL), and the
organic layer was dried over MgSO4. The solvent was evaporated
to give pure products 5a–d and 6a–d. Products were fully charac-
terized by elemental analysis and NMR data.17
17. For 5a: 92%, yellow oil, 1H NMR d 8.06 (d, 1H, JHH = 6 Hz, H-3), 6.38 (dd, 1H,
Acknowledgments
4
3
3JHH = 6 Hz, JHH = 1 Hz, H-4), 5.94 (s, 1H, H-6), 3.53 (t, 2H, JHH = 7 Hz, H-9),
1.56 (sx, 2H, JHH = 7 Hz, H-10), 0.87 (t, 3H, JHH = 7 Hz, H-11). 13C NMR d 179.2
3
The authors thank the Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq- Process No. 306938/2007-3 and
No 476158/2007-9) for the financial support and PIBIC-fellowship
(for J. L. Malavolta). The financial support from Fundação de Apoio
a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) is also
acknowledged.
(q, JCF = 35 Hz, C-7), 170.2 (C-2), 156.1 (C-5), 136.4 (C-3), 128.7 (C-4), 116.0 (q,
JCF = 291 Hz, C-8), 95.7 (C-6), 41.2 (C-9), 21.5 (C-10), 11.2 (C-11). MS m/z (%)
233 (M+, 32), 164 (100), 136 (30). Compound 5b: 87%, yellow oil, 1H NMR d
3
3
8.13 (d, 1H, JHH = 6 Hz, H-3), 7.37–7.18 (m, 5H, Ph), 6.52 (dd, 1H, JHH = 6 Hz,
4JHH = 1 Hz, H-4), 5.99 (s, 1H, H-6), 4.83 (s, 2H, H-9). 13C NMR d 179.1 (q,
JCF = 35 Hz, C-7), 170 (C-2), 155.4 (C-5), 136.7 (C-3), 134.9, 129, 128.7, 128.1,
127 (Ph), 115.8 (q, JCF = 291 Hz, C-8), 96.9 (C-6), 43.2 (C-9). MS m/z (%) 281(M+,
100), 212 (13), 184 (30), 91 (69). Compound 5c: 94%, white solid, mp 98–99 °C,
3
1H NMR d 8.28 (d, 1H, JHH = 6 Hz, H-3), 7.6–7.21 (m, 5H, Ph), 6.58 (dd, 1H,
3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 5.95 (s, 1H, H-6). 13C NMR d 179.4 (q, JCF = 36 Hz,
C-7), 169.3 (C-2), 156.5 (C-5), 136.5 (C-3), 132.2, 129.9, 129.3, 128.6, 123.4
(Ph), 115.8 (q, JCF = 291 Hz, C-8), 97.3 (C-6). MS m/z (%) 267 (M+, 39), 198 (100),
170 (51), 144 (9), 77 (28). Compound 5d: 94%, yellow oil. 1H NMR d 8.28 (d, 1H,
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.07.073.
3
3JHH = 6 Hz, H-3), 7.71 (m, 2H, Ar), 7.12 (m, 2H, Ar), 6.58 (dd, 1H, JHH = 6 Hz,
4JHH = 1 Hz, H-4), 5.94 (d, 1H, H-6). 13C NMR d 179.4 (q, JCF = 36 Hz, C-7), 169 (C-
2), 156 (C-5), 136.7 (C-3), 133.2, 131.2, 129.4 (Ar), 128.6 (C-4), 123.4 (Ar), 115.7
(q, JCF = 291 Hz, C-8), 97.4 (C-6). MS m/z (%) 347 (M++2, 25), 345 (M+, 25), 276
(58), 248 (9), 169 (100). Compound 6a: 89%, white solid, mp 52–53 °C. 1H NMR
d 8.18 (d, 1H, 3JHH = 6 Hz, H-3), 6.43 (dd, 1H, 3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 6.37
References and notes
1. Flores, A. F. C.; Flores, D. C.; Oliveira, G.; Pizzuti, L.; Silva, R. M. S.; Martins, M. A.
P.; Bonacorso, H. G. J. Braz. Chem. Soc. 2008, 19, 184–193.
2. Piovesan, L. A. Ph.D. Dissertation, Federal University of Santa Maria, 2009.
3. Martins, M. A. P.; Sinhorin, A. P.; Rosa, A.; Flores, A. F. C.; Wastowski, A. D.;
Pereira, C. M. P.; Flores, D. C.; Beck, P.; Freitag, R. A.; Brondani, S.; Cunico, W.;
Bonacorso, H. G.; Zanatta, N. Synthesis 2002, 2353–2357.
4. Tsolomiti, G.; Tsolomitis, A. Tetrahedron Lett. 2004, 45, 9353–9355.
5. Pinheiro, S.; da Silva, R. C., Jr.; Souza, A. S.; Carneiro, J. W.; Muri, E. M. F.;
Antunes, O. A. C. Tetrahedron Lett. 2009, 50, 2402–2404.
4
3
3
(d, 1H, JHH = 1 Hz, H-6), 3.64 (t, 2H, JHH = 7 Hz, H-9), 1.65 (sx, 2H, JHH = 7 Hz,
H-10), 0.95 (t, 3H, JHH = 7 Hz, H-11). 13C NMR d 179.4 (C-7), 170 (C-2), 155.3 (C-
5), 135.9 (C-3), 128.2 (C-4), 96.7 (C-6), 96 (C-8), 41 (C-9), 21.6 (C-10), 11.2 (C-
11). MS m/z (%) 281 (M+, <5), 164 (100), 145 (14), 122 (31). Compound 6b: 93%,
white solid, mp 92–94 °C. 1H NMR d 8.17 (d, 1H, JHH = 6 Hz, H-3), 7.38–7.20
3
(m, 5H, Ph), 6.5 (dd, 1H, 3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 6.33 (s, 1H, H-6), 4.86 (s,
2H, H-9). 13C NMR d 179.3 (C-7), 169.9 (C-2), 154.5 (C-5), 136.2 (C-3), 135.3,
128.9, 128.1, 128, 127.2 (Ph), 97.6 (C-6), 96.5 (C-8), 43.3 (C-9). MS m/z (%) 331
(M++2, 12), 329 (M+, 13), 294 (46), 212 (59), 184 (5), 91 (100). Compound 6c:
88%, white solid, mp 130–132 °C, 1H NMR d 8.33 (d, 1H, 3JHH = 6 Hz, H-3), 7.56–
6. Taylor, J. M.; Abell, A. D. J. Org. Chem. 1993, 58, 14–15.
7. Abell, A. D.; Oldham, M. D.; Taylor, J. M. J. Org. Chem. 1995, 60, 1214–1220.
8. Langer, P.; Döring, M. Synlett 2001, 1437–1439.
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7.26 (m, 5H, Ph), 6.56 (dd, 1H, JHH = 6 Hz, JHH = 1 Hz, H-4), 6.31 (d, 1H,
4JHH = 1 Hz, H-6). 13C NMR d 179.7 (C-7), 169.3 (C-2), 155.8 (C-5), 136.1 (C-3),
132.5, 129.8 (Ph), 129 (C-4), 128.1, 127.7 (Ph), 97.9 (C-6), 96.4 (C-8). MS m/z (%)
317 (M++2, <5), 315 (M+, <5), 198 (100), 170 (23), 144 (9), 77 (28). Compound
6d: 86%, yellow solid, mp 127–130 °C, 1H NMR d 8.33 (d, 1H, 3JHH = 6 Hz, H-3),
7.69 (m, 2H, Ar), 7.15 (m, 2H, Ar), 6.56 (dd, 1H, JHH = 6 Hz, JHH = 1 Hz, H-4),
6.31 (d, 1H, H-6). 13C NMR d 179.6 (C-7), 169 (C-2), 155.2 (C-5), 136.3 (C-3),
133.1, 131.5, 129.3 (Ar), 128.1 (C-4), 123.1 (Ar), 98 (C-8), 96.3 (C-6). MS m/z (%)
395 (M++2, <5), 393 (M+, <5), 276 (100), 248 (8), 169 (30).
9. Singh, V.; Saxena, R.; Batra, S. J. Org. Chem. 2005, 70, 353–356.
10. Blaszczyk, E.; Krawczyk, H.; Janecki, T. Synlett 2004, 2685–2688.
11. Nagasaka, T.; Koseki, Y.; Kusano, S. Tetrahedron Lett. 1998, 39, 3517–3520.
12. Dieter, R. K.; Lu, K. Tetrahedron Lett. 1999, 40, 4011–4014.
13. Pizzuti, L. Ph.D. Dissertation, Federal University of Santa Maria, 2008.
14. Crystallographic data for compound 3d have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication
number 740176. Copies of the data can be obtained free of charge, on
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